Indium replica for metallurgical examination

The work herein described was accomplished in the Solid States Section of the Physics Division at the Oak Ridge National Laboratory during June, July and August of 1948. The purpose of this work was to discover a feasible technique for making metallurgical examinations of highly radioactive samples. The solution of this problem was sought through the use of a replica technique.http://archive.org/details/indiumreplicform1094531646Lieutenant Commander, United States NavyApproved for public release; distribution is unlimited

Democratic Nationalistic Privilege and the Exclusion of Europe\u27s Gypsy

Europe is the world’s best example of a group of countries offering similar levels of political freedom, tolerance, and economic prosperity and security. Following the fall of Communism, Europe began to outpace the rest of the planet on aggregated indicators of development, and, according to Freedomhouse.org, only two of the world’s forty seven “not free” countries, Belarus and Russia, can be found on this continent. The Roma, frequently mislabeled as “Gypsies,” are among the few troubled populations residing in Europe. In the comprehensive 2006 Final Report on the Human Rights Situation of the Roma in Europe, one Romani man describes being a “Gypsy” in the following statement: “There is a lot of prejudice and discrimination against Roma in my country. We find it hard to do things that others take for granted. It\u27s difficult to get your child into a good school and higher education is often an unattainable goal. There are problems with the housing because no-one wants Roma in their neighborhood. We encounter problems because of who we are every day and we want to do something about it because our government turns a blind eye to racial crimes committed against Roma. Quite often we have problems with the police, they suspect we all must be criminals. Even if you manage to graduate, it\u27s really hard to get a job. People assume that Roma are crooks and will steal or swindle. We don\u27t want to be given preferential treatment, we just want the same opportunities as everyone.” Although there has been a great deal written about the Romani people, there has been very little cooperation between academic fields. Studies surrounding the political realities affecting the Roma ignore the role culture plays. Anthropologists have done a reasonably comprehensive job summarizing distinctions between the dominant culture and that of the Roma, but generally do not discuss how those discrepancies can make life more difficult. Economists cite how a failure to assimilate into the formal economy affects the Roma, but rarely address the sizable barriers to assimilation. Development experts are attuned to the difficulties of life in Roma communities, but rarely expand their focus enough to make statements about the entire population. Finally, a disregard for a painful history which includes slavery, exile, and genocide results in unfair terms for the conversation about the Roma. This gap in scholarship contributes to the way European populations think about the Roma. Policymakers and voters can accept individual instances wherein a member of this population might be excluded or disenfranchised, but rarely does the whole picture come into focus. Many are reluctant to believe that in the progressive, democratic meritocracy that is modern Europe one population could be at such a disadvantage, and interactions with Romani citizenry only serve to reinforce the racist idea that they are somehow to blame for their exclusion. I argue that the exclusion of Europe’s Roma populations stems from three different arenas- culture, politics, and history. These factors culminate in a pervasive and deep-rooted system of, what I have called a democratic nationalistic privilege enjoyed by the majority populations in Europe. The advantages of living in a free and developed part of the world are withheld from the Roma, and ingrained racism exacerbates the problem. My report intends to raise awareness of the Roma’s plight and help bring about a dialogue aimed at more fair treatment. Changing the terms of conversation surrounding the Roma may be a first step in eliminating their status as an exception, unable to access the prosperity enjoyed by the rest of Europe. Rather than the social exclusion they experience, changing the understanding and context of the Roma\u27s position can contribute to their simple ability to live alongside fellow citizens harmoniously

Atorvastatin with or without an Antibody to PCSK9 in Primary Hypercholesterolemia

Background Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces LDL cholesterol levels. Methods We performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to receive 8 weeks of treatment with 80 mg of atorvastatin daily plus SAR236553 once every 2 weeks, 10 mg of atorvastatin daily plus SAR236553 once every 2 weeks, or 80 mg of atorvastatin daily plus placebo once every 2 weeks and were followed for an additional 8 weeks after treatment. Results The least-squares mean (±SE) percent reduction from baseline in LDL cholesterol was 73.2±3.5 with 80 mg of atorvastatin plus SAR236553, as compared with 17.3±3.5 with 80 mg of atorvastatin plus placebo (P Conclusions In a randomized trial involving patients with primary hypercholesterolemia, adding SAR236553 to either 10 mg of atorvastatin or 80 mg of atorvastatin resulted in a significantly greater reduction in LDL cholesterol than that attained with 80 mg of atorvastatin alone. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials. gov number, NCT01288469.

Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia:Results of a 24week, double-blind, randomized Phase 3 trial

Background:Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy. Methods In a Phase 3, randomized, double-blind, double-dummy study (NCT01644474), patients (low-density lipoprotein cholesterol [LDL-C] 100–190 mg/dL, 10-year risk of fatal cardiovascular events = 1%–&lt;5% [systemic coronary risk estimation]) were randomized to ezetimibe 10 mg/day (n = 51) or alirocumab 75 mg subcutaneously (via 1­mL autoinjector) every 2 weeks (Q2W) (n = 52), with dose up-titrated to 150 mg Q2W (also 1 mL) at week 12 if week 8 LDL-C was = 70 mg/dL. Primary endpoint was mean LDL-C % change from baseline to 24 weeks, analyzed using all available data (intent-to-treat approach, ITT). Analyses using on-treatment LDL-C values were also conducted.Results: Mean (SD) baseline LDL-C levels were 141.1 (27.1) mg/dL (alirocumab) and138.3 (24.5) mg/dL (ezetimibe). The 24-week treatment period was completed by 85% of alirocumab and 86% of ezetimibe patients. Least squares mean (SE) LDL-C reductions were 47 (3)% with alirocumab versus 16 (3)% with ezetimibe (ITT; p &lt; 0.0001) and 54 (2)% versus 17 (2)% (on-treatment; p &lt; 0.0001).At week 12, before up-titration, alirocumab 75 mg Q2W reduced LDL-C by 53 (2)% (on-treatment). Injection site reactions were infrequent (&lt; 2% and &lt; 4% of alirocumab and ezetimibe patients, respectively). Conclusions: Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide = 50% LDL-C reduction in the majority of the patients. Adverse events were comparable between groups.</p

Relationship between alirocumab, PCSK9, and LDL-C levels in four phase 3 ODYSSEY trials using 75 and 150 mg doses

BACKGROUND: Alirocumab is a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9). OBJECTIVE: Changes in PCSK9, alirocumab, and low-density lipoprotein cholesterol (LDL-C) levels were assessed after treatment with alirocumab at doses of 75 or 150 mg every 2 weeks (Q2W). METHODS: Data were analyzed from 4 phase 3 trials (MONO; COMBO II; FH I; LONG TERM); all but MONO enrolled patients on statins. Three trials evaluated alirocumab 75 mg Q2W, with possible dose increase to 150 mg Q2W at week 12 based on week 8 LDL-C; LONG TERM studied alirocumab 150 mg Q2W. RESULTS: Patients on background statin therapy had higher mean baseline free PCSK9 concentrations vs patients not on statin. After alirocumab administration, increased alirocumab concentrations were associated with dramatic reductions in circulating free PCSK9, resulting in significant LDL-C reductions and a corresponding increase in inactive PCSK9:alirocumab complex. Alirocumab dose increase was associated with a further lowering of PCSK9 and LDL-C. Patients with higher baseline LDL-C levels (>160 mg/dL) were more likely to have their dose increased. LDL-C reductions with alirocumab were consistent between patients with baseline PCSK9 levels above or below the median when the dose increase strategy was used. When started as alirocumab 150 mg Q2W, patients with PCSK9 levels above vs below the median had a greater LDL-C reduction. CONCLUSIONS: Alirocumab-induced changes in PCSK9 and LDL-C levels were consistent with the known physiologic relationship between PCSK9, LDL receptor, and LDL-C levels, as well as statin-induced increases in PCSK9 production. (C) 2019 National Lipid Association. Published by Elsevier Inc.Peer reviewe

A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia

BACKGROUND Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/ kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab. METHODS We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52. RESULTS Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain. CONCLUSIONS At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks